Urban Health StudyA cross-sectional study of San Francisco Bay area injection drug users enrolled >2,400 participants. This study will allow us to make genetic comparisons between long-time IDUs who failed to become infected with HCV and otherwise similar HCV-infected subjects. We will also compare subjects who are chronically infected with HBV or HCV to those with resolved infection. We examined the association between drug injection and HHV-8 infection among these San Francisco Bay area IDUs. HHV-8 infection was relatively common among women (10%), heterosexual men (10%), and men who have sex with men (23%). Seroprevalence increased with longer duration of drug use in all three groups and the findings were not explained by sexual behavior or demographic differences. These results are consistent with blood-borne transmission of HHV-8 among IDUs. SEN viruses are a newly discovered family of blood-borne DNA viruses. Their relationship to disease remains to be determined, but they may play a role in liver disease or response to treatment for HCV. San Francisco Bay area IDUs had high rates of SEN virus strains A (46%), C/H (36%) and D (10%). The prevalence of these viruses varied demographically..HCV seroprevalence decreased markedly between 1987 and 1998-2000 among new initiates to injection drug use in the San Francisco Bay area. This decrease occurred after the implementation of prevention activities among this population.Among HCV-infected injection drug users, there is an inverse relationship between chronic HBV and chronic HCV becomes greater with more years of drug use or older age.HALT-C TrialThe HALT-C trial is designed to evaluate the safety and efficacy of long-term PEG-IFN-a2a for treatment of chronic hepatitis C in patients who did not respond to previous interferon therapy (with or without ribavirin) and who have evidence of hepatic fibrosis by biopsy (Ishak 3-6). During a 24 week lead in phase, enrolled patients are treated with PEG-IFN-a2a and Ribavirin (Pegasys, Roche). HALT-C subjects who are positive for HCV RNA at week 20 (non-responders) are randomized to either long-term treatment with PEG-IFN-a 2a (maintenance phase) or to no additional therapy. Patients without detectable HCV RNA levels in their serum at week 20 remain on treatment through week 48 and are followed until week 72. Patients without detectable HCV RNA at week 72 (at least 24 weeks after treatment is discontinued) are defined as sustained virologic responders (SVR). We will compare host genetic polymorphisms in HALT-C non-responders to HALT-C participants who achieved a SVR after re-treatment with PEG-IFN and Ribavirin. HALT-C non-responders will be defined as patients with non-response to re-treatment at week 20.